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The aim of this study is to develop a simple and applicable HPLC method for the detection of cefpodoxime acid (CFA) in rabbit plasma after oral administration of cefpodoxime proxetil (CFP) loaded chitosan–alginate (CH-ALG) beads formulation. CFP is a prodrug that is deesterified in vivo to its active metabolite CFA to exhibit antibiotic activity. Chromatographic separation of CFA and internal standard (IS) was achieved by a RP18(C18), Phenomenax®100, (250 × 4.6 mm) with the mobile phase consisting of (0.02 mol/l (20 mM) ammonium acetate solution and acetonitrile (92:8, v/v, pH = 4.6) at a flow rate of 1.0 ml/min. The method was validated according to the requirements of US-FDA guidelines for bioanalytical method validation. The linear regression analysis for the calibration plots showed good linear relationship (R2 = 0.9905) in the working concentration range of 0.5–50 μg/ml. The limits of detection and quantification (S/N = 3) were 0.069 and 0.136 μg/ml. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The analyte was found to be stable after a number of stability studies. The proposed HPLC method was successfully applied to pharmacokinetic study in rabbits for CFP loaded CH-ALG beads and marketed immediate release (IR) tablets. All pharmacokinetic parameters were assessed.

A fast and sensitive UHPLC-DAD method was developed and subsequently validated for determination of cefetamet pivoxil hydrochloride in the presence of its degradation products. The chromatographic separation was carried out on a Waters Acquity BEH C18, (2.1 x 100 mm, 1.7 µm) column. The mobile phase was composed of 0.1% formic acid and acetonitrile (40 : 60, v/v) at the flow rate 0.7 mL/min. The detection wavelength was 265 nm and the temperature was 30 °C. Cefetamet pivoxil hydrochloride was susceptible to degradation under the influence of sodium hydroxide, hydrochloric acid and in the conditions of increased temperature and relative humidity. However, it was stable after irradiation, in increased temperature in dry air and in the presence of oxidizing agent. The developed UHPLC-DAD method was linear over the concentration range of 10-240 µg/mL (r2 = 0.9999; n = 12). The obtained RSD values were less than 2%, demonstrating that the described procedure is precise. The accuracy was also confirmed (mean recoveries were 97.79-102.08%). Under applied chromatographic conditions LOD and LOQ values were 2.08 mg/mL and 6.29 mg/mL, respectively. The proposed method was successfully applied in determination of cefetamet pivoxil hydrochloride in aqueous solutions as well as in the solid state.

We tested a phenyl mannitol broth containing ceftizoxime and aztreonam (PHMB + ) for detection of methicillin-resistant Staphylococcus aureus (MRSA) with reference MRSA strains and, subsequently, with clinical samples ( n = 1,098). All reference MRSA strains induced color change in PHMB + after 24 to 72 h of incubation. In a clinical setting, 40 MRSA strains were detected with PHMB + , compared with only 23 detected with a routine method. Thus, this selective broth significantly ( P < 0.001) improved the rate of MRSA detection.

Selective screening media for extended-spectrum beta-lactamase (ESBL)-producing bacteria are needed to guide antibiotic therapy and institute appropriate infection control measures. This study evaluates a selective cefpodoxime-incorporated chromogenic agar (CCA) medium for the detection of ESBLs from clinical specimens. The medium was formulated specifically for this study. For all culture-positive urine samples and wound swabs from intensive care unit (ICU) patients, CCA was compared with standard laboratory testing procedures and HPA/BSAC guidance on ESBL detection. The CCA medium was also evaluated for ESBL faecal carriage from patients on ICU and the haematology ward. These patients had no prior evidence of colonisation or infection with ESBL-producing bacteria. All ESBL isolates underwent minimum inhibitory concentration (MIC) testing to cefpodoxime. The Miles and Misra method and the ecometric methods were used to quality control the microbiological performance of the CCA medium, which proved satisfactory. A total of 750 specimens were examined (690 urines, 40 faeces, 20 wound swabs). From urine cultures, 92 suspect colonies were followed up. Eighteen were cefpodoxime-resistant on routine disc testing and all were confirmed subsequently as ESBL-positive. Conventional laboratory methods identified only two urinary ESBLs. Wound cultures revealed two suspect colonies, both of which were ESBL-positive and were also detected by routine methods. Faecal samples produced 10 suspect colonies, six of which were ESBL-positive. All ESBLs had cefpodoxime MICs >10 mg /L (75% were >256 mg/L). Thus, primary conventional culture methods cannot be relied upon to detect suspect ESBL-producing bacteria.

This paper deals with the extensive investigation of molecular interaction between third generation cephalosporin antibiotic, Cefpodoxime Acid (CA) and Human Mixtard Insulin (HMI) in an aqueous medium through ultrasonic, dilute solution viscometric (DSV) and spectral [UV-vis, Attenuated total reflection (ATR)-FT IR] methods at various blend compositions of the drug and insulin at three different (303K, 310K and 313K) temperatures. This is an attempt to unravel the possibility of drug induced hypoglycemic effect. The existence of solute-solute interaction in aqueous solutions of CA and HMI is established from the variation of ultrasonic velocity and other acoustical parameters with blend composition. DSV method is used to confirm the range of blend composition at which the molecular interaction is significant. The conclusions drawn from ultrasonic and DSV methods are further established by the UV-vis and ATR- FT IR spectral studies of ternary mixtures at different blend compositions. Further, the existing interactions suggest the possibility of cefpodoxime acid induced hypoglycemia which is discussed based on the structural aspects of the two components.

ChromID ESBL agar and Brilliance ESBL agar were compared for the isolation of extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae from 298 stools. These had comparable sensitivity and selectivity for the 116 positive samples. Pre-enrichment with cefpodoxime and extending incubation to 48hours after direct plating both significantly increased sensitivity but reduced selectivity of both agars.

The purpose of this research was to assessment of antimicrobial activity and in vitro/in vivo evaluation of cefpodoxime proxetil extended-release (ER) tablet for once daily administration. The tablets were prepared using combination of biodegradable polysaccharides including hydroxypropyl methylcellulose and sodium alginate as matrix material to achieve pH-independent ER release. The tablets were found within the permissible limits for various physicochemical parameters. The in vitro drug release showed that the drug was released over a period of 24h in a sustained release manner. The drug release followed Higuchi kinetics as these plots showed the highest linearity (R(2)=0.9833), but a close relationship was also observed with zero-order kinetics (R(2)=0.9088) and the drug release mechanism was found to be of anomalous or non-Fickian type. Further, in vitro drug release was assessed by antimicrobial assay and it revealed that drug release through 24h periods was above the MIC. In vivo investigation in rabbits showed ER pharmacokinetic profile of cefpodoxime from the matrix tablets. A good correlation of drug absorption in vivo and drug release in vitro (R(2)=0.9785) was observed. These results suggested that the investigated CFP matrix tablets have a potential for extended-release dosage forms.

The purpose of this study was to investigate the presence of Aeromonas hydrophila at commonly used water collection points on the River Njoro and to determine the in-vitro antimicrobial susceptibility and plasmid profiles of isolates. In total, 126 samples were collected and 36.5% of them were positive for A. hydrophila. The A. hydrophila were recovered on membrane filters, cultured on Trypticase Soy agar, Bile aesculin agar and Aeromonas Medium agar. They were further characterized using cytochrome oxidase and API 20E tests. Detection of drug susceptibility was determined using modified disc diffusion method to ampicillin (25 ìg), cefaclor (30 ìg), ceftizoxime (30 ìg), cefixime (5 ìg), cefazidime (30 ìg), gentamicin (200 ìg), streptomycin (25 ìg), chloramphenicol (50 ìg), nalidixic acid (30 ìg) and ciprofloxacin (1 ìg). Most of the isolates showed multi-drug resistance to two or more antibiotics. Chloramphenicol, nalidixic acid, ciprofloxacin, cefazidime and cefixime were the most sensitive drugs with 100% efficacy whereas ampicillin, cefaclor and streptomycin were the most resistant drugs having 100, 67 and 50 resistance, respectively. There was low resistance against ceftizoxime (16.7%) and gentamicin (23.3%). These results indicates that all A. hydrophila isolated from River Njoro had complete resistance to ampicillin and showed variable resistance to cefaclor, streptomycin, gentamycin and ceftizoxime. R-plasmids were extracted from multi-drug resistance strains and separated by agarose gel (0.8%) electrophoresis for profiling. Plasmid profiling revealed that most of the multi-drug resistant isolates contained one plasmid of 21.0 kb. Although some strains exhibited different antimicrobial resistance patterns, all of their plasmids were of the same size (21.0 kb). However, there were no plasmids in the antimicrobial sensitive isolates. This study also indicates that plasmid 21.0 kb is common in A. hydrophila and is important for antimicrobial resistance and virulence. Further studies are required to ascertain the role of this plasmid as a virulence marker.Key words: Aeromonas hydrophila, antimicrobial resistance, plasmid profile.

Osteomyelitis is an infectious disease located in the bone or bone marrow. Long-circulating and pH-sensitive liposomes containing a technetium-99m-labeled antibiotic, ceftizoxime, (SpHL-(99m)Tc-CF) were developed to identify osteomyelitis foci. Biodistribution studies and scintigraphic images of bone infection or non infection-bearing rats that had been treated with these liposomes were performed. A high accumulation in infectious foci and high values in the target-non target ratio could be observed. These results indicate the potential of SpHL-(99m)Tc-CF as a potential agent for the diagnosis of bone infections.

WOS: 000321693400023 PubMed: 22630073 Cord blood has numerous facilities for life and used in many different areas. Cord blood contains many different catalytic proteins including antioxidant enzymes. Here we purified human cord blood glutathione reductase (hcbGR), glutathione S-transferase (hcbGST) and human cord blood glutathione peroxidase (hcbGPx) from human cord blood erythrocytes and analyzed the inhibition effects of the antibiotics incorporating cefuroxime, ceftriaxone, ceftizoxime and cefoperazone, on these enzymes. K-I values for the drugs ranged from 10.42 to 28.72 mu M for hcbGR, 32.7 to 244.8 mu M for hcbGPx, and 32.39 to 267.3 mu M for hcbGST. Cefuroxime caused the highest inhibition on all enzymes with K-I values of 10.42, 32.39, 32.7 mu M for hcbGR, hcbGST, and hcbGPx, respectively. All drugs displayed non-competitive inhibition regardless of their structures. Since these drugs are often used during pregnancy, identification of possible undesired impacts on various parameters has a great importance for pharmacological and medical applications.

Lipid based drug delivery systems have gained prominence in last decade for drugs with dissolution rate limited oral bioavailability.To improve the solubility, permeability and oral bioavailability of cefpodoxime proxetil, β-lactam antibiotic. It is BCS Class IV drug having solubility 400 µg/mL and 50% oral bioavailability.Self-nanoemulsifying drug delivery system (SNEDDS) using various surfactant and cosurfactants such as tween 80, tocopheryl polyethylene glycol succinate (TPGS), propylene glycol and Capmul MCM as oil phase were prepared. Ternary phase diagrams were constructed to identify stable microemulsion region. Percent transmittance studies helped to shortlist the surfactant-cosurfactant combination.Tween 80 and TPGS as surfactants and Capmul MCM as oil phase were found to produce stable nanoemulsions. Five formulations of SNEDDS had globule size of 55-60 nm and zeta potential of -4 to -11 mV. Self-emulsification time was between 221 and 370 s, while viscosity was dependent on composition of SNEDDS. Cloud point was above 70°C which indicated the retention of in vivo self-emulsifying properties. Average flux for cefpodoxime proxetil (CP) and SNEDDS was 0.104 and 0.985 µg/cm(2) min. Permeability was 19.72 and 206 for CP and SNEDDS. Liquid SNEDDS spray coated onto micropellets of microcrystalline cellulose (18-20#) were analysed by scanning electron microscope (SEM), self-emulsification and in vitro dissolution. A 5.36-fold increase in area under curve AUC(0-∞) was observed for CP-SNEDDS than plain drug. Minimum inhibitory concentration (MIC) was lower for SNEDDS. Liquid and SNEDDS micropellets were stable under accelerated conditions.SNEDDS formulations led to improved oral bioavailability due to enhanced solubilization of selected drug.

In this study, resistance improvement of E.coli , isolated from patients that applied to clinics in Kahramanmaras, against β-Lactam antibiotics, was investigated. Antibiograms were carried out to determine the resistance of E.coli strains. For antibiyogram, with ‘The Kirby-Bower‘s Disk Diffusion Method’ was applies. In result, Ceftizoxime (%70.58) and Imipenem (%55.88 ) were appeared as the most effective antibiotics about inhibition of E.coli growing and Ampicilin (%98.52) was appeared as the least effective antibiotics.

Most urinary tract includes (UTIs) in children are monomicrobic, often caused by Escherichia coli. Evidence on risk factors for UTI in children is limited. UTIs were associated with constipation, encopresis, bladder instability, and infrequent voiding in some studies but not in a cohort of febrile children younger than two years. In this study we evaluated antibiogram pattern E. coli isolated from urinary tract infection in Iranian girl children’s.Materials and MethodsThe search was laboratory and performed in DEY laboratory in 2010 year in Isfahan, a total 702 urinary children samples, cultured and study with microbiological methods.Antibiotic susceptibility was performed with antibiotic susceptibility standard disc diffusion agar.ResultsAccording to result of antibiogram test, respectively 40(90.90%), 32(66.66%),16 (38.095%), 34(70.069%),10 (22.72%),18 (37.5%),19 (42.22%), 8(16.32%) and 26 (61.90%) of Escherichia coli strains Isolated was resistant to Nitrofurantoion, Ceftizoxime,Cephalothin,Ciprofloxacin,Tetracycline,Co-Trimoxazole,Nalidixic Acid, Amoxycillin and Gentamicin.DiscussionOral antibiotics are as effective as parenteral therapy in randomized trials.The optimal duration of antibiotic therapy has not been established,but one-day therapies have been shown to be inferior to longer treatment courses. Undiagnosed or untreated UTIs can lead to kidney damage,especially in kids younger than six year. Establish systems for monitoring antimicrobial resistance in hospitals and the community and link these findings to resistance and disease surveillance data is fundamental to developing treatment guidelines accurately and to assessing the effectiveness of interventions appropriately.

This study aims to prove the complexation of cefpodoxime proxetil (CP) by hydroxypropyl-β-cyclodextrin (HP-β-CD) in the presence of sodium carboxymethyl cellulose (Na CMC), and makes a comparison of commercial tablets by dissolution and antimicrobial activity studies. The CP--HP-β-CD complex was prepared by kneading method and characterized by SEM, FTIR and DSC. The solubility method was used to investigate the effect of HP-β-CD and Na CMC on the solubility of CP. The complex tablets were prepared using direct compression method. Dissolution studies were performed with complex tablets and commercial tablets in pH 1.2, 4.5, 6.8 and 7.4 buffer solutions. It was observed that complexation occurred in all formulations, and HP-β-CD is able to increase CP solubility and dissolution rate of CP was improved from complex tablets, when compared with commercial tablets. Furthermore, the antimicrobial activity studies revealed that the CP--HP-β-CD complex and complex tablets were shown to have more effective antimicrobial activity than commercial tablets. It is evident from the results that complexation with HP-β-CD in the presence of Na CMC is feasible way to prepare a more efficient tablet formulation with improved dissolution and antimicrobial activity.

Cefpodoxime proxetil (CFP), an oral third-generation cephalosporin, is a prodrug that is de-esterified in vivo to its active metabolite, cefpodoxime acid (CFA). Therefore, this study aimed to develop a facile and efficient one-pot reaction for selective and sensitive determination of CFA and its prodrug (CFP). The method was based on single-step reaction between CFP or CFA and 1,2-naphthoquinone-4-sulfonate (NQS) as a selective derivatizing reagent in alkaline medium without heating, extraction or reduction steps as usual for NQS derivatization reactions. The fluorescence of the formed NQS-derivative was monitored directly at emission wavelength of 440 nm after excitation at 330 nm. The method can easily be implemented in plating facilities by operators and/or incorporated in on-line derivatization reaction. The correlation coefficients of 0.9991 and 0.9984 were obtained in the concentration ranges of 50–2000 ng mL−1 for CFA and CFP, respectively. The detection limits were 9.17 and 9.48 ng mL−1 for CFA and CFP, respectively. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for their efficient and sensitive determinations. The developed method was successfully applied for selective determination of CFP in pure form and in pharmaceutical dosage forms as well as CFA in human urine after single dose of CFP without prior need for separation. The method is valuable for quality control laboratories for monitoring of CFP and its active metabolite CFA.

The aim of the present study was to develop a fast, sensitive and reliable method for rapid screening of cephalosporin injectable dosage forms namely ceftazidime and ceftizoxime to the detection of counterfeit and substandard drugs that might be illegally commercialized. Ceftazidime, ceftizoxime and cefixime (IS) were separated in a X-Terra RP-18 column (250 × 4.60 mm ID × 5 μ) and DAD detector set at 290 and 260 nm. The mobile phase consisted of a mixture of methanol:water 20:80 (v/v) at a flow rate of 1.0 mL min−1. Additionally, in order to find the optimum pH value of separation the pK a values of studied compounds were determined by using two different methodologies. Aqueous pK a values of studied compounds have been determined by UV-spectrophotometry and liquid chromatography were used for the determination and direct characterization of the dissociation constants by using the dependence of the capacity factor on the pH of the mobile phase in 20% (v/v) methanol–water binary mixture in which separation was performed. The pH of the mobile phase was adjusted with 25 mM H3PO4 to 3.2. The method was shown to be linear, sensible, accurate, and reproducible over the range of analysis and it can be used to pharmaceutical formulations containing a single active ingredient within a short analysis time.

Background—Administration of an oral cephalosporin allowed advancement of the dosage of oral irinotecan. This study investigates whether administration of an oral cephalosporin increases the maximum tolerated dose (MTD) of intravenous irinotecan. Procedure—Irinotecan was administered intravenously on Days 1– 5 and Days 8 – 12 of a 21day cycle with continuous oral cefpodoxime starting 2 days prior to irinotecan. Cohorts of 3 to 6 pediatric patients with refractory solid tumors were enrolled at 4 dosage levels, starting at the single-agent irinotecan MTD of 20 mg/m 2 /dose. Results—The 17 evaluable patients received 39 courses of therapy. None of the patients treated with 20 mg/m 2 /dose experienced dose-limiting toxicity (DLT). One of 6 patients treated at 30 mg/ m 2 /dose experienced dose-limiting neutropenia. Two of 3 patients treated with 45 mg/m 2 /dose and 2 of 5 treated with 40 mg/m 2 /dose experienced dose-limiting diarrhea, with associated dehydration and anorexia. Two unconfirmed partial responses were observed after one course in a patient with Ewing sarcoma and one with paraganglioma. A child with refractory neuroblastoma had disease stabilization through 12 courses of therapy. Median (range) systemic exposure to SN-38 at the MTD (30 mg/m 2 /dose) was 67 ng-h/mL (36 to 111 ng-h/mL).

Amoxicillin is a beta-lactam antibiotic frequently used inveterinary medicine. Amoxicillin activity is time dependent, thatis death of bacteria is related to drug concentration and length oftime bacteria are exposed to the drug (Drusano, 2004; McKellaret al., 2004). Amoxicillin may be administered associated withother treatments, including antiemetic agents, giving raise topotential pharmacological interactions. We have proved in dogsthat the total exposure of oral cephalexin was enhanced whenthe antibiotic was administered after metoclopramide (Pradoset al., 2007). On the contrary, both the peak serum concentra-tion and the disposition curve of a prodrug of ceftizoxime werenot affected when the dogs were pretreated with this prokineticagent (Mori et al., 2001).The purpose of this study was to investigate whether previousadministration of metoclopramide affects amoxicillin pharmaco-kinetics after its oral administration to dogs as well as whetherthese changes impair its predicted clinical efficacy. In addition, asage-related changes may affect drugs disposition in geriatricpatients (Harvey & Paddleford, 1999; Dowling, 2005), two ageddogs were included in this study.The institutional animal use and care committee approved thestudy protocol. Five adult (age 5.0 ± 3.0 years) and two aged(15.0 years) beagle dogs received a single oral dose of 25 mg⁄kgamoxicillin trihydrate (500 mg⁄5 mL oral aqueous suspension,Amoxidal 500, Roemmers) with and without an intravenous0.5 mg⁄kg metoclopramide previous (20 min) treatment, with a2-week washout period between phases. The subjects were all ingood health, and none of the dogs had a history of allergy tobeta-lactamsorhadreceivedantibiotics4 weekspriortoenteringthe experience. Dogs were randomly assigned to treatment, andaged dogs were treated in opposite groups.Blood samples were collected from the jugular vein atpredetermined times up to 11.5 h postadministration. Plasmawas separated by centrifugation at 1500 g for 10 min and wasstored at 4 C until analysis within 72 h after collection.Amoxicillin concentrations were calculated by a microbiologicalprocedure (Bennet et al., 1966). Standard curves were preparedin canine plasma and run simultaneously with test samples. Thecalibration curve was linear over the concentration range tested(0.390–50 lg⁄mL, r

Klebsiella pneumoniae has been associated with different types of infections and one of the most important aspects of Klebsiella is the emergence of multi-drug resistant strains particularly those involved in nosocomial diseases. Fifty - nine clinical isolates were collected from different parts of India. Most of the samples were recovered from respiratory, urinary tract infection and pus cases which were followed by biochemical characterization. Twenty confirmed K. pneumoniae isolates were further tested for antimicrobial drug sensitivity and almost fifty percent of them were found to be multidrug resistant. As per our statistical data, all confirmed K.pneumoniae isolates were resistant to carbenicillin and one among them recovered from sputum sample of a pneumonic patient was resistant to all the antimicrobial agents tested except exhibiting a partial susceptibility to amikacin. In our studies we found that K.pneumoniae strains from clinical cases were highly susceptible to quinolones and the aminoglycoside, amykacin and gentamycin. At the same time over 60 % strains were resistant to chloramphenicol and tetracycline. We also found that 28 to 76 % of them were resistant to cephalosporins (ceftizoxime and cefotaxime). On the basis of statistical binomial test we conclude that piperacillin, carbenicillin, ofloxacine ampicillin, co-trimoxazole and chloramphenicol were significantly resistant, whereas cefotaxime and tetracycline were found to be moderately resistant against Klebsiella pneumoniae.

To investigate whether or not the combined ultrasound and antibiotic treatment is effective against chlamydial infection, a new ultrasound exposure system was designed to treat chlamydia-infected cells. First, the minimum inhibitory concentrations of antibiotics against Chlamydia trachomatis were determined. Infected cultures were treated with antibiotics then sonicated at intensity of 0.15 or 0.44 W/cm(2) with or without Bubble liposomes. After 48 or 72 h after infection, chlamydial inclusions were stained and examined by fluorescence microscopy. The internalization of dextran-fluorescein conjugates by ultrasound irradiation with Bubble liposomes was observed by fluorescence microscopy. The results showed that application of nanobubble-enhanced ultrasound caused no significant effect on cell viability and chlamydial infectivity. However, Doxycycline (1/2 MIC) or CZX (1.0 μg/ml) in combination with nanobubble-enhanced ultrasound dramatically reduced the number of inclusions compared with that administered with antibiotics only. Bubble dose-dependent synergy was also observed. After ultrasound irradiation at intensity of 0.44 W/cm(2) on the presence of Bubble liposomes, 10% of HeLa cells were observed to have internalized the dextran molecules. This study suggests the possibility of using nanobubble-enhanced ultrasound to deliver antibiotic molecules into cells to eradiate intracellular bacteria, such as chlamydiae, without causing much damage to the cells itself.

The purpose of this study was to validate a reliable analytical method for pharmacokinetic study of ceftibuten in human plasma by high performance liquid chromatography (HPLC) system with UV detection. Ceftizoxime was used as the internal standard. After plasma sample was precipitated with acetonitrile and dichloromethane, the supernatant was directly injected into the HPLC system. Separation was performed on a Capcell Pak C18 UG120 column (4.6 mm × 250 mm, 5 μm particles) with a mobile phase of acetonitrile/50 mM ammonium acetate (5: 95, v/v) and UV detection at a wavelength of 262 nm. The intra- and inter-day precision expressed as the relative standard deviation was less than 15%. The lower limit of quantification was 0.5 hg/mL of ceftibuten using 0.5 mL of plasma. The calibration curve was linear in concentration range of 0.5–30 μg/mL (r 2 = 0.9998). The mean accuracy was 96–102%. The coefficient of variation (precision) in the intra- and inter-day validation was 0.9–3.9 and 0.9–2.4%, respectively. The pharmacokinetics of ceftibuten was evaluated after a single oral administration of 400 mg to healthy volunteers. The AUC0–9 h, c max, T max, and T 1/2 were 86.6 ± 12.7 μg h/mL, 18.4 ± 1.5 μg/mL, 2.63 ± 0.83 and 2.65 ± 0.41 h, respectively. The method was demonstrated to be highly reproducible and feasible for pharmacokinetic studies of ceftibuten in eight volunteers after oral administration (400 mg as ceftibuten).

The administration of cephalosporin group antibiotics in patients with post-surgical appendicitis is necessary to prevent postoperative wounds. This pharmacoeoconomic study was conducted retrospectively in the period of 1 January to 31 December 2015 in RSUD Subang for the purpose of determining the effectiveness of drugs and the cost of antibiotic use of ceftriaxone, cefotaxime, and ceftizoxime injection by Cost Effectiveness Analysis method. The subject of the patient was 78 people. Based on Average Cost Effectiveness Ratio (ACER), the smallest value is ceftriaxone Rp 729.124 / day, while the result of Cost Effectiveness plane with cefotaxime as standard drug, ceftriaxone occupies quadrant IV and ceftizoxime occupies quadrant I. The result of Incremental Cost Effectiveness Ratio (ICER) calculation obtained by difference of value equal to Rp 106.347 / day hence can be concluded that antibiotic injection of cefotaxime as standard injection antibiotics used by RSUD Subang can be replaced by antibiotic injection of ceftizoxim by adding cost Rp 106.347 / day but need attention to resource especially funds owned and should be selected if sufficient resources are available.

A preliminary study was conducted on the sensitivity pattern of microorganisms against antibiotics at the intensive care unit of Fatmawati Hospital Jakarta. Retrospective, secondary data were collected on results of antibiotics sensitivity tests and kind of microorganisms of 205 patients during the years 2001 – 2002. Pathogenic species found were Pseudomonas sp. Klebsiella sp. Escherichia coli, Streptococcus β haemolyticus, Staphylococcus epidermidis and Staphylococcus aureus. The pattern of resistance showed that pathogenic microorganisms were most resistant agains ampicillin, amoxycillin, penicillin G, tetracycline and chloramphenicol. The highest sensitivity levels were shown by fosmicin, amikacin, ceftriaxone to Pseudomonas sp. netilmicin, amikacin, ceftriaxone to Klebsiella sp. ceftriaxone, amikacin, ceftizoxime to Escherichia coli.

Cefetamet is a potent antibiotic to treat respiratory and urinary tract infections. To improve oral bioavailability, it is administered as a prodrug, cefetamet pivoxyl hydrolyzed by esterase following absorption. A quantification method using a mass spectrometry was developed for the determination of cefetamet in human plasma. After a protein precipitation with acetonitrile, the analytes were chromatographed on a reversed-phase C₁₈ column and detected by a tandem mass spectrometer with electrospray ionization. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of the cefetamet in plasma after a single oral administration of 500 mg cefetamet pivoxyl.

Poorly water-soluble drugs such as cefpodoxime proxetil (400 μg/ml) offer a challenging problem in drug formulation as poor solubility is generally associated with poor dissolution characteristics and thus poor oral bioavailability. According to these characteristics, preparation of cefpodoxime proxetil microparticle has been achieved using high-speed homogenization. Polymers (methylcellulose, sodium alginate, and chitosan) were precipitated on the surface of cefpodoxime proxetil using sodium citrate and calcium chloride as salting-out agents. The pure drug and the prepared microparticles with different concentrations of polymer (0.05–1.0%) were characterized in terms of solubility, drug content, particle size, thermal behavior (differential scanning calorimeter), surface morphology (scanning electron microscopy), in vitro drug release, and stability studies. The in vivo performance was assessed by pharmacokinetic study. The dissolution studies demonstrate a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of cefpodoxime proxetil from optimized microparticle was attributed to the wetting effect of polymers, altered surface morphology, and micronization of drug particles. The optimized microparticles exhibited excellent stability on storage at accelerated condition. The in vivo studies revealed that the optimized formulations provided improved pharmacokinetic parameter in rats as compared with pure drug. The particle size of drug was drastically reduced during formulation process of microparticles.

Background: Pseudomonas aeruginosa is 1 of the major agents of nosocomial infections in burn centers. Our objectives were to determine the genetic diversity of P. aeruginosa isolated from burn patients. Methods: One hundred thirty-one P. aeruginosa isolates were collected from the burn center of Shahid Motahhari Hospital in Tehran. Phenotypic screening for drug susceptibility was performed by disk diffusion method according to Clinical Laboratory Standards Institute guidelines, and genetic diversity of all isolates was determined by the pulsed-field gel electrophoresis (PFGE) technique. Results: Antimicrobial susceptibility testing showed that the majority of P. aeruginosa strains were resistant to ceftizoxime (87%) and aztreonam (80.2%). Pulsed-field gel electrophoresis revealed 11 profiles in which environmental strains were included in PFGE1 and PFGE7 patterns. The major PFGE profile was PFGE1 containing 18 (42.9%) MDR isolates and including an environmental MDR bacterium. Conclusions: Our findings highlighted that further attention needs to be focused on the disinfection of this burn unit. * PFGE : pulsed-field gel electrophoresis MDR : multidrug-resistant BU : burn units MP : multi-purpose UPGMA : unweighted pair group method using arithmetic averages

Minimum inhibitory concentrations (MICs) of 20 antimicrobial agents for 41 isolates of Burkholderia mallei from natural outbreaks of equine glanders were determined by agar dilution. All isolates were intrinsically resistant to ampicillin (MIC 90 ≥128). Resistance to other antimicrobials was as follows: 95.1% to amoxicillin and cephradine, 85.4% to cefuroxime and norfloxacin, 68.3% to ceftizoxime and ceftriaxone, 61.1% to ceftiofur, 58.5% to oxytetracycline, 41.5% to ciprofloxacin, 58.5% to roxithromycin, 17.1% cefotaxime, and 12.2% clarithromycin. Overall resistance patterns revealed that 17% of isolates were simultaneously resistant to amoxicillin, cephradine, cefuroxime, ceftizoxime, ceftriaxone and norfloxacin. None of the isolates were resistant to amoxicillin-clavulanic acid, doxycycline, chloramphenicol, gentamicin or trimethoprim-sulphadiazine. Mode MICs for these antimicrobials were 2, 1, 8, 4 and 1 μg/ml, respectively. A majority of the isolates (∼ 94%) were susceptible to both enrofloxacin and ofloxacin. These data provide an updated perspective on susceptibility profiles of current strains of B. mallei in an endemic area.

Cefpodoxime proxetil (CP) is a prodrug, the third generation cephem-type broad-spectrum antibiotic administered orally. However, CP was found to be a poorly water-soluble drug with low bioavailability when orally administered. In the present investigation, the spray-dried cefpodoxime proxetil nanosuspension (SDN) was prepared. The physicochemical properties were characterized by rheological evaluation, particle size measurement and its distribution, dynamics of reconstitution, in-vitro dissolution testing, surface morphology, surface area and pore size measurements. The pharmacokinetic study of SDN, in comparison to a marketed cefpodoxime proxetil for oral suspension (MS), was also performed in rabbits after a single oral dose. It was found that SDN exhibited a significant decrease in t(max), a 1.60-fold higher area under curve (AUC) and 2.33-fold higher maximum plasma concentration (C(max)) than MS.

Recently, hospital-associated as well as community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strains showing a low level of resistance to oxacillin have emerged worldwide, and as a result, a highly sensitive method to detect MRSA has become more important. To prevent MRSA being overlooked, some selection agar media have recently been developed. We evaluated six commercially available selection agar media in regard to the detection of 35 borderline MRSA (BOMRSA) strains which were mecA-positive but showed low resistance to oxacillin. The MIC values of oxacillin differed between the broth dilution method and the agar dilution method, and 11 of the 35 BOMRSA strains were judged as sensitive by the broth dilution method and 14 of the 35 strains were judged as sensitive by the agar dilution method. Thirty-two of the 35 strains were also judged as sensitive by an oxacillin disk diffusion test. Moreover, there was no consistent pattern of resistance to the tested beta-lactams among the BOMRSA strains. Some commercially available selection media designed for the detection of MRSA contain a beta-lactam antibiotic; oxacillin, ceftizoxime, or cefoxitin, and we evaluated media containing each of these agents. The detection sensitivities of cefoxitin-based agar media, such as CHROMagar MRSA and MRSA ID, for BOMRSA were 100% at 24-h culture. On the other hand, the media containing oxacillin or ceftizoxime gave lower results at 24 h, suggesting that, possibly, BOMRSA strains may not to be able to grow on these media. These results suggest that cefoxitin-based agar media should be recommended for the first-round screening of BOMRSA.

Although group B streptococcus (GBS) has been considered to be uniformly susceptible to β-lactams, the presence of GBS with reduced penicillin susceptibility (PRGBS) was recently confirmed genetically. We developed a feasible and reliable method for screening PRGBS in clinical microbiology laboratories using a combination of ceftibuten, oxacillin, and ceftizoxime disks.

Simultaneous drug-induced immune hemolytic anemia (DIIHA) caused by multiple drugs is rare. We report a case of a patient who developed DIIHA caused by 2 drugs. The patient's serum exhibited agglutination of ceftizoxime- or sulbactam-coated red blood cells (RBCs; via a drug-adsorption mechanism) and of uncoated RBCs in the presence of sulbactam (via an immune-complex mechanism). Although ceftizoxime is known to exhibit a positive reaction by an immune-complex method with or without reactivity with drug-coated RBCs, this patient's antibodies were reactive only against drug-coated RBCs. On the other hand, sulbactam, which is known to cause hemolytic anemia by nonimmunologic protein adsorption, exhibited positive reactions in tests with both drug-coated RBCs and in the presence of sulbactam. This is the first report of DIIHA due to a sulbactam-cefoperazone combination and the fourth report of DIIHA due to ceftizoxime. Owing to the patient's complicated laboratory results, DIIHA was suspected only at a late stage. We propose that for the prompt diagnosis of DIIHA, tests for all possible causative drugs should be conducted by 2 methods.

The microcalorimetric method has been used to study the effects of cefpiramide and ceftizoxime sodium on the E. coli growth. The results revealed that these two cephalosporins may alter the metabolic way of the E. coli. Moreover, the lethal doses of cefpiramide and ceftizoxime sodium are 2.000 and 0.2000 μg mL−1, respectively. Combining with the relationships between growth rate constant (k), the maximum power output (P m ), the time corresponding to the maximum power output (t m ) and cephalosporins concentration (C), one can draw the conclusion that the ceftizoxime sodium has a stronger inhibition effects on the growth of E. coli than that of cefpiramide and they both have the possibility to induce the drug fever.

Infant mice infected with Candida albicans by the oral-intragastric route became colonized in the gut and were persistently colonized into adulthood. Faecal levels of Candida were correlated with total gastrointestinal Candida and provided a useful means of detecting yeast overgrowth or elimination. Antibacterial agents promoting Candida overgrowth when given by the oral or parenteral route included ceftriaxone, augmentin and cefoperazone. Ceftizoxime had less effect. Ceftazidime and latamoxef produced raised levels only by the oral route. Gentamicin, vancomycin and metronidazole did not affect the Candida levels. Dosing with some antibacterials promoted an increase in gastrointestinal Candida and invasion to a greater extent than immunosuppression. Antifungal therapy to reduce gastrointestinal colonization was investigated using amphotericin B, nystatin, ketoconazole, intraconazole and fluconazole. Fluconazole was most effective at reducing faecal Candida.

Fine particles of cefpodoxime proxetil (CPD) were prepared using an Aerosol Solvent Extraction System (ASES) with supercritical CO 2 . The resulting primary particles were approximately 0.1–0.2 μm in size and were almost spherical in shape. The secondary particles were approximately 0.2–0.6 μm in size and had irregular shapes. The larger particle size and irregular shapes were due to the agglomeration of the primary particles. The effects of solvent type, CO 2 -to-CPD solution weight ratio, and CPD solution concentration on the extent of agglomeration were investigated. As a result, the use of ethyl acetate and acetone as solvents also reduced the degree of agglomeration. The degree of agglomeration was reduced with the use of a high CO 2 -to-solution weight ratio, and a low solution concentration. In particular, spherical particles, approximately 0.1–0.4 μm in size, were obtained when a 10.0 wt% CPD solution was used. As a result of dissolution study, almost 90% of the processed CPD had dissolved within 10 min. The recovery yield of the CPD powder reached approximately 80% using a membrane filter.

The aim of this study was to investigate the prevalence and antimicrobial susceptibility of bacterial strains isolated from tracheal specimens obtained from pediatric patients admitted to a major children hospital in Tehran, in 2007. Tracheal specimens were cultured on the appropriate bacteriological media. Bacterial isolates were identified by standard biochemical and serological tests. Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Pseudomonas spp. was identified as the most prevalent bacterial isolate (32%) followed by Staphylococcus aureus (27.6%). Thirty strains (16%) were identified as Klebsiella spp., 18 (9.6%) as Enterobacter spp. and the rest belonged to coagolase negative Staphylococci, Streptococcus viridans, Acinetobacter spp., Escherichia coli and Neisseria spp. All Pseudomonas spp. were resistant to ampicllin, kanamycin and ceftizoxime. Staphylococcus and Klebsiella spp. showed high degree of resistance to 40% of examined antibiotics.

Background. The concept of antimicrobial prophylaxis (AMP) did not exist in Japan until recently. Therefore, postoperative administration of antimicrobial drugs has long been practiced under the pretext of prophylaxis against surgical site infection (SSI). In recent years, however, the concept of AMP and prophylactic countermeasures against SSI, based on evidence of the effectiveness of AMP, has gradually spread in Japan. From 2000 onward, we have undertaken prophylactic countermeasures against SSI in patients undergoing spinal surgery referring to the Guideline for Prevention of Surgical Site Infection published by the Centers for Disease Control and Prevention in 1999. The purpose of this study was to investigate the type of AMP that would be appropriate for spinal surgery and the manner in which it should be used. Methods. The subjects were 1415 patients who underwent spinal surgery at our department from January 1990 to March 2008. The patients were classified into four groups according to the method of AMP administration: group 1, AMP was employed for 7 days, only postoperatively; group 2, initial AMP dosing was administered at the time of anesthesia induction, followed by administration of AMP for 5 days, including the day of the operation; group 3, initial AMP dosing was administered at the time of anesthesia induction, and AMP was administered for 3 days, including the day of the operation; group 4, the initial dosing was administered at the time of anesthesia induction, and AMP was administered for 2 days, including the day of the operation. The frequency of SSI was assessed in the four groups. Results. The frequencies of SSI in groups 1−4 were 2.6% (14/539), 0.9% (5/536), 0% (0/257), and 0% (0/83), respectively. Thus, the frequency of SSI decreased as the duration of the AMP administration period decreased. Conclusions. As a result of thorough implementation of preventive measures against perioperative occurrence of infections, which included additional preoperative and intraoperative administration of AMP, the incidence of SSI could be decreased despite shortening the duration of AMP administration to 2 days.

Background and Objectives. Extended spectrumβ-lactamase (ESBL) production is increasing all over the world, and organisms other thanE. coliandK. pneumoniaeare acquiring this character. ESBL production is detectable by automation, E-test, double disk diffusion (DDD), and PCR. This study aimed to determine the prevalence of ESBL production among clinical isolates of gram-negative rods, and to evaluate the effectiveness of augmentation of clavunate with Cefotaxime, Ceftazoxime, Aztreonam, Ceftriaxone, and Cefpodoxime in detecting ESBL production.Methods. 472 clinical gram-negative isolates identified by standard methods were tested for ESBL-production by (DDD) method using six cephalosporins and amoxicillin-clavulinate discs.Results. 108/472 (22.9%) of the isolates were ESBL producers, and were prevalent in tertiary care hospitals. 88.2% ofE. cloacae, 71.4% ofK. pneumoniae, 28.6% ofK. oxytoca, 12.5% ofC. freundii, 11.1% ofA. calcoacceticus, and 10.8% ofE. coliwere ESBL producers. The DDD test demonstrated some variations in the efficacy of the different cephalosporins in detecting all the ESBL producers. The inclusion of ceftizoxime discs increased the efficacy of the test. It is concluded that ESBL-producing bacteria were prevalent among our hospitalized patients, and involved genera other thanKlebsiellaandEscherichia, and the inclusion of ceftizoxime increased the efficacy of ESBL detection by the DDD test.

Purpose To investigate inflammatory (zymosan) and infectious (Staphylococcus aureus) processes in experimental models in rats using technetium-99m-labeled ceftizoxime (CFT). Methods Male Wistar rats were used for the development of the inflammatory (zymosan) and infectious (S. aureus) processes in the medullary cavity of the left tibia. Sterile saline was used for the control group. At 48 h after induction of the processes, the animals were anesthetized and scintigraphic images were acquired at 1, 2, 4, and 6 h after intravenous injection of 0.1 ml of 99mTc-CFT (55 MBq). Quantitative analysis of the scintigraphic images was performed by counting the radioactivity in the regions of interest. Samples of tibia were taken for histopathological examination. Results The images showed that 99mTc-CFT presented higher tropism to infectious foci than with the inflammatory site. The average value of the target/nontarget ratio of the 99mTc-CFT was significantly higher in the infected (2.40+/-0.22) than in the inflamed tibia (1.50+/-0.05) and the control group (1.05+/-0.04) for all of the investigated times. The histological data showed a similar inflammatory response for both the S. aureus and zymosan groups. Conclusion The 99mTc-CFT presented a high tropism and retention for an infected region in this model of osteomyelitis, thereby constituting an interesting strategy to distinguish aseptic from septic sites.

The pharmacokinetic profile of ceftriaxone was studied in female healthy goats, induced hepatopathic and nephropathic goats after a single intravenous dose at 50 mg kg(-1). Ceftriaxone persisted for 2 h in plasma of hepatopathic goats compared to 1 h of healthy goats, but the kinetic behaviour followed 'one-compartment open model' in both healthy and hepatopathic goats. Mean value of t((1/2))beta (0.32 +/- 0.008 h) was significantly higher in hepatopathic goats compared to healthy goats (0.19 +/- 0.002 h). Ceftriaxone was recovered at 24 h in urine of hepatopathic goats but it could not be detected in urine of healthy goats. However, its metabolite ceftizoxime was present in urine of healthy goats but not in urine of hepatopathic goats. On the other hand ceftriaxone persisted for 2 h in plasma of kidney damaged goats with significant higher concentration compared to healthy goats but kinetic behaviour followed 'one Compartment open model'. Ceftizoxime was identified with an adequate plasma concentration from 8 h to 12 h post dosing in nephropathic goats. Elimination halflife (t(1/2)beta) of Elimination ceftriaxone (0.38 +/- 0.01 h) in nephropathic goats increased significantly compared to healthy goats (0.19 +/- 0.002 h). Ceftriaxone, not the metabolite ceftizoxime was recovered at 24 h and 48 h post dosing in urine of nephropathic goats, while only ceftizoxime not ceftriaxone was detected in urine of healthy goats.

The efficacy of β-lactams is thought to be dependent on the time that the unbound concentrations exceed the MIC ( fT >MIC). However, the pharmacokinetic/pharmacodynamic index (PDI) that correlates best to the selection of resistance is not yet clear. The selection of ceftizoxime (CZX)-resistant Enterobacter cloacae mutant strains during the development of murine mixed-infection abscesses was studied to determine the PDI that is important for the emergence of resistance and the PDI value needed for the prevention of resistance. Studies were carried out 24 h after inoculation with Bacteroides fragilis ATCC 23745 and E. cloacae 22491. Six to 1,536 mg of CZX/kg of body weight/day given every 2 h (q2h), q4h, q6h, or q8h was started 30 min before inoculation and continued for 24 h. Resistant mutants were isolated to determine mutant frequencies (MF). The fT >MIC varied from 9 to 98% for E. cloacae , the peak concentration (unbound fraction) was 0.6 to 578 mg/liter, and the area under the concentration-time curve (unbound fraction) ( f AUC) was 1.9 to 553 mg·h/liter. The f AUC-to-MIC ratio best explained the in vivo efficacy. CZX-resistant B. fragilis and E. cloacae mutants were isolated from untreated controls at an MF of 10 −5 to 10 −7 . The MF of resistant B. fragilis did not increase during therapy. The selection of resistant E. cloacae strains at an MF of 10 −1 to 10 −2 was related to the fT >MIC and the ratio of f AUC to MIC following an inverse U shape. However, the ratio of f AUC to MIC was the stronger driver of resistance. The highest MFs were 0.7 to 0.9 at an f AUC-to-MIC ratio of approximately 250. We conclude that the ratio of f AUC to MIC is the PDI that correlated best to the in vivo efficacy of CZX and probably also to the emergence of resistant E. cloacae mutants. An f AUC-to-MIC ratio of 1,000 was needed to prevent the emergence of this resistance.

Received 3 December 2006; returned 26 February 2007; revised 20 March 2007; accepted 18 April 2007Objectives: Aminopenicillin-induced exanthema poses a problem in the management of infectious dis-eases. Due to theoretically possible immunological cross-reactivity, all b-lactam drugs, i.e. penicillins,penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics(macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and theiruse increases medical costs. Moreover, their use contributes to the increasing bacterial resistance toantibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-inducedexanthema may receive specific b-lactams for future antibiotic therapy.Methods: Skin testing followed by oral challenges to identify b-lactams that are tolerated by patientsdespite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to ami-nopenicillins.Results: Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to amino-penicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefix-ime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin.Conclusions: The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicil-lins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challengetests can be helpful to determine individual cross-reactivity.Keywords: drug challenge, drug provocation, non-IgE-mediated allergic hypersensitivity, skin tests

Large-scale chromosomal inversions (455 to 535 kbp) or deletions (266 to 320 kbp) were found to accompany spontaneous loss of beta-lactam resistance during drug-free passage of the multiresistant Staphylococcus haemolyticus clinical strain JCSC1435. Identification and sequencing of the rearranged chromosomal loci revealed that ISSha 1 of S. haemolyticus is responsible for the chromosome rearrangements.

Self-nanoemulsifying drug delivery systems (SNEDDS) were developed with the objective to overcome problems associated with the delivery of cefpodoxime proxetil (CFP), a poorly bioavailable high dose antibiotic having pH dependant solubility. Solubility of CFP in oily phases and surfactants was determined to identify components of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify selected oily phases. Ternary phase diagrams were constructed to identify area of nanoemulsification for the selected systems. The influence of CFP and the pH of dilution medium on the phase behavior of selected system were assessed. The globule size of optimized CFP SNEDDS in various dissolution media was determined to check the effect of pH on its behavior. The optimized CFP SNEDDS needed surfactant content less than 40% and yielded nanoemulsion of mean globule size 170 nm, which was not affected by the pH of dilution medium. The optimized SNEDDS released CFP completely within 20 min irrespective of the pH of dissolution medium.

ChromID ESBL agar and Brilliance ESBL agar were compared for the isolation of extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae from 298 stools. These had comparable sensitivity and selectivity for the 116 positive samples. Pre-enrichment with cefpodoxime and extending incubation to 48 hours after direct plating both significantly increased sensitivity but reduced selectivity of both agars., Highlights • Two chromogenic agars were compared for the isolation of ESBL Enterobacteriaceae. • Both agars had comparable sensitivity and selectivity. • Sensitivity after direct plating was higher when incubated for 48 versus 24 hours. • Using pre-enrichment with 24-hour incubation further increased the sensitivity. • There was a loss of selectivity after 48-hour incubation for all methods

Metal implants are used frequently in orthopedic procedures and the occurrence of subclinical low-virulence infection is difficult to diagnose. The objective of this study was to examine the hypothesis that peri-prosthetic subclinical infections may be diagnosed effectively in a murine model system using scintigraphic imaging with (99m)Tc-labeled ceftizoxime.A sample population of 3-mo old Wistar rats (mean weight 327 g) was divided randomly into a control group (n=6), which received sterile implants, and an experimental group (n=6), which received implants contaminated with Staphylococcus aureus strain ATCC6538-P. Animals were anesthetized and femoral titanium implants were fixed beneath muscle tissue in left hind limbs. Three weeks after surgery, animals were injected with (99m)Tc-ceftizoxime solution (62.9 MBq) and scintigraphic images were obtained at 3.5 and 6.5 h after tracer injection.According to the scintigraphic images, the radiopharmaceutical showed affinity for the operated thigh areas of experimental animals but not for those of the control group. There was no difference between the control and experimental groups regarding the amount of radioactivity in the regions of interest measured at 3.5 h after injection of radiolabeled antibiotic, but the between-group difference determined at 6.5 h after treatment was statistically significant (p=0.026). Moreover, the level of radioactivity recorded in resected thigh tissues derived from experimental animals was greater than that of the control group (p=0.035).(99m)Tc-ceftizoxime scintigraphy can localize preferentially periprosthetic-infected areas adjacent to metal implants in a murine model. Furthermore, the radiolabeled antibiotic appears to be capable of detecting alterations in the micro-environment close to the implant and of reaching the bacteria attached to the implant surface.

The process of degradation was studied by using an HPLC–DAD method. Two degradation products were identified with a hybrid ESI-Q-TOF mass spectrometer. The influence of temperature and relative air humidity (RH) on the stability of cefoselis sulfate was investigated. In the solid state at increased RH the degradation of cefoselis sulfate was an autocatalytic reaction of the first order with respect to substrate concentration while in dry air was first-order reaction depending on the substrate concentration. The kinetic and thermodynamic parameters of degradation were calculated.

Diego dos Santos Ferreira,1 Fernanda Alves Boratto,1 Valbert Nascimento Cardoso,2 Rogéria Serakides,3 Simone Odília Fernandes,2 Lucas Antônio Miranda Ferreira,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy, 2Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, 3Veterinary School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Abstract: Osteomyelitis is a progressive destruction of bones caused by microorganisms. ­Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate specificity. By contrast, radiolabeled antibiotics could improve selectivity, since they are specifically recognized by the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery systems with high affinity for bones could improve the overall uptake. In this work, long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime were prepared and their ability to identify infectious foci (osteomyelitis) in animal models was evaluated. The effect of the presence of PEGylated lipids and surface-attached alendronate was evaluated. The bone-targeted long-circulating liposomal 99mtechnetium–ceftizoxime showed higher uptake in regions of septic inflammation than did the non-long-circulating and/or alendronate-non-coated liposomes, showing that both the presence of PEGylated lipids and alendronate coating are important to optimize the bone targeting. Scintigraphic images of septic or aseptic inflammation-bearing Wistar rats, as well as healthy rats, were acquired at different time intervals after the intravenous administration of these liposomes. The target-to-non-target ratio proved to be significantly higher in the osteomyelitis-bearing animals for all investigated time intervals. Biodistribution studies were also performed after the intravenous administration of the formulation in osteomyelitis-bearing animals. A significant amount of liposomes were taken up by the organs of the mononuclear phagocyte system (liver and spleen). Intense renal excretion was also observed during the entire experiment period. Moreover, the liposome uptake by the infectious focus was significantly high. These results show that long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime have a tropism for infectious foci. Keywords: bone targeting, radiolabeled antibiotics, scintigraphic imaging, bone infection diagnosis

Penicillins remain first-line agents for treatment of group B Streptococcus ( Streptococcus agalactiae ; GBS) infections; however, several reports have confirmed the existence of GBS with reduced penicillin susceptibility (PRGBS). Because no selective agar plates for detection of PRGBS are available to date, in this investigation, we developed the selective agar plate for detection of PRGBS. We used 19 genetically well-confirmed PRGBS isolates and 38 penicillin-susceptible GBS isolates identified in Japan. For preparation of trial PRGBS-selective agar plates, we added 1 of antimicrobial agents (among oxacillin, ceftizoxime, and ceftibuten) to a well-established GBS-selective agar plate. Among 12 trial PRGBS-selective agar plates, Muller–Hinton agar containing 128μg/mL ceftibuten with 5% sheep blood, 8μg/mL gentamicin, and 12μg/mL nalidixic acid was the most appropriate selective agar for PRGBS, showing 100% sensitivity and 81.6% specificity. In cases of potential nosocomial spread of PRGBS, the selective agar plate could be useful and reliable.